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Haematology and Blood Transfusion Vol. 26<br />

<strong>Modern</strong> Trends in Human Leukemia IV<br />

Edited by Neth, Gallo, Graf, Mannweiler, Winkler<br />

© Springer-Verlag Berlin Heidelberg 1981<br />

Myeloid Dysplasia: the Histopathology of Preleukemia *<br />

A. Georgii, J. Thiele, and K. -F. Vykoupil<br />

The clinical term "preleukemia" is understood<br />

as an alteration of the bone marrow and<br />

peripheral blood preceding overt acute myeloid<br />

leukemia (AML, review by Saarni and<br />

Linman 1973). However, in the majority of<br />

cases the diagnosis is only a retrospective one,<br />

derived from many mostly clinical and cytogenetic<br />

investigations (Fisher et al 1973 ; Dreyfus<br />

1976; Linman and Bagby 1978; Pierre 1978).<br />

The aim of our study was to determine w hether<br />

there are characteristic lesions of the bone<br />

marrow preceding obvious leukemia and if<br />

wether those lesions are similar in cases<br />

evolving AML or CML later on.<br />

Among more than 15,000 biopsies of the<br />

bone marrow which were performed during<br />

the last 10 years 195 patients were selected<br />

whose examina ti on of the bone marrow was<br />

initiated by the clinical assumption of a possible<br />

preleukemic state. This selection following<br />

the suggested clinical dia gnosis of so-called<br />

preleukemia inherits a problem: there may be<br />

no clear cut separation between a preleukemic<br />

state of leukemia and a myeloproliferative<br />

disorder or CML in early stage or chronic<br />

megakaryocytic-granulocytic myelosis<br />

(CMGM, see Georgii 1979).<br />

Are-evaluation of the semithin sections of<br />

these bone cylinders displayed two different<br />

categories of dis orders : 62 patients had either<br />

nonneoplastic lesions (leukemoid reaction,<br />

12; hyperergic myelitis (mostly rheumatic),<br />

23; pernicious anemia, 11; panmyelophthisis,<br />

3 and other diseases 13 or early stage CML 35<br />

and oligoblastic leukemia 5. The remaining<br />

second category of 93 patients showed distinc-<br />

* Supported by the Deutsche Forschungsgemeinschaft<br />

(DFG Ge 121/19)<br />

tive and identical morphological features of<br />

the bone marrow which probably correspond<br />

to hemopoietic dysplasia of Linman and Bagby<br />

(1978), but should be rather called myeloid<br />

dysplasia, MD, (Thiele et al. 1980a): Histopathology<br />

is characterized by a hypercellularity<br />

(Fig 1a) in most of the cases, a frequently<br />

occurring megaloblastoid and at least macrocytic<br />

differentiation of erythropoiesis (Figs.<br />

1 b, 2a). There are many sideroblasts of the<br />

granular type and a shift to the left of the<br />

neutrophilic granulopoiesis which displays the<br />

so called pseudo-Pelger-Huet anomaly of maturation<br />

(Figs. 2a,b). It should be emphasized<br />

that there is no increase in blasts along the<br />

peritrabecular generation zones of granulopoiesis.<br />

Megakaryocytes are not only increased<br />

but exhibit abnormal cells such as frequent<br />

naked nuclei, micromegakaryocytes, and too<br />

many immature forms (Figs. 1a, 2b). The<br />

myeloid stroma contains a patchy edema and<br />

often a remarkable perivascular plasmacytosis<br />

(Figs. 1a, 2c). Electron microscopy of these<br />

cell confirms these findings and extends our<br />

results of an abnormal cellular differentiation<br />

in MD (for details see Thiele et al. to be<br />

published a).<br />

Gf these 93 patients with the histomorphology<br />

of MD at the time of their first and initial<br />

biopsy, sequential corings of the iliac crest (up<br />

to five times in periods ranging from 2 months<br />

to 3112 years) as weIl as review of the clinical<br />

records revealed that 26 cases evolved obvious<br />

leukemia and the remaining 67 did not show<br />

apparent leukemia until now (Table 1).<br />

Initial main clinical symptoms were mostly<br />

unspecific, ranging from fatigue, loss of weight,<br />

easy bleeding, and pallor to physical findings<br />

such as dermal hemorrhage, slight to moderate<br />

hepatomegaly, and minimal splenomegaly.<br />

34

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